Therapeutic compounds and compositions

Patent metadata

Field	Value
Publication number	US-12428376-B2
Application number	US-202318507013-A
Country	US
Kind code	B2
Filing date	Nov 10, 2023
Priority date	Jun 29, 2009
Publication date	Sep 30, 2025
Grant date	Sep 30, 2025

Abstract

Compounds and compositions comprising compounds that modulate pyruvate kinase M2 (PKM2) are described herein. Also described herein are methods of using the compounds that modulate PKM2 in the treatment of cancer.

First claim

What is claimed is:

1. A compound of formula (I)

or a pharmaceutically acceptable salt thereof, wherein
W, X, Y and Z are each independently selected from CH or N;
D and D 1 are independently selected from a bond or NR b ;
A is optionally substituted bicyclic heteroaryl;
L is a bond, —C(O)—, —(CR c R c ) m —, —OC(O)—, —(CR c R c ) m —OC(O)—, —(CR c R c ) m —C(O)—, —NR b C(S)—, or —NR b C(O)—;
R 1 is selected from alkyl, cycloalkyl, aryl, heteroaryl, and heterocyclyl; each of which is substituted with 0-5 occurrences of R d ;
each R 3 is independently selected from halo, haloalkyl, alkyl, hydroxyl and —OR a or two adjacent R 3 taken together with the carbon atoms to which they are attached form an optionally substituted cyclyl;
each R a is independently selected from alkyl, acyl, hydroxyalkyl and haloalkyl;
each R b is independently selected from hydrogen and alkyl;
each R c is independently selected from hydrogen, halo, alkyl, alkoxy and haloalkoxy or two R c taken together with the carbon atoms to which they are attached form an optionally substituted cycloalkyl;
each R d is independently selected from halo, haloalkyl, haloalkoxy, alkyl, alkynyl, nitro, cyano, hydroxyl, —C(O)R a , —OC(O)R a , —C(O)OR a , —SR a , —NR a R b and —OR a , or two R d taken together with the carbon atoms to which they are attached form an optionally substituted heterocyclyl;
n is 0, 1, or 2;
m is 1, 2 or 3; and
h is 0 and g is 2 or h is 2 and g is 0.

2. The compound of claim 1 , wherein W, X, Y and Z are CH.

3. The compound of claim 1 , wherein D is NR b and D 1 is a bond.

4. The compound of claim 1 , wherein L is a bond, —(CR c R c ) m —, —NR b C(O)—, —(CR c R c ) m —C(O)—, —C(O)—, or —O(CO)—.

5. A pharmaceutical composition comprising a compound of claim 1 or a pharmaceutically acceptable salt thereof.

Assignees

• Agios Pharmaceuticals Inc

Inventors

• Salituro Francesco G
• Saunders Jeffrey O
• Yan Shunqi

Classifications

• C07D295/192

  from aromatic carboxylic acids · CPC title

• Y02P20/582

  Recycling of unreacted starting or intermediate materials · CPC title

• C07D417/14

  containing three or more hetero rings · CPC title

• C07D417/12

  linked by a chain containing hetero atoms as chain links · CPC title

• C07D409/12

  linked by a chain containing hetero atoms as chain links · CPC title